rs867915

chr7-111730580-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363540.2(DOCK4):c.5481+1646C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 152,162 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.045 (181 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100

Genes affected

DOCK4 (HGNC:19192): (dedicator of cytokinesis 4) This gene is a member of the dedicator of cytokinesis (DOCK) family and encodes a protein with a DHR-1 (CZH-1) domain, a DHR-2 (CZH-2) domain and an SH3 domain. This membrane-associated, cytoplasmic protein functions as a guanine nucleotide exchange factor and is involved in regulation of adherens junctions between cells. Mutations in this gene have been associated with ovarian, prostate, glioma, and colorectal cancers. Alternatively spliced variants which encode different protein isoforms have been described, but only one has been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK4	NM_001363540.2	c.5481+1646C>G		intron_variant		ENST00000428084.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK4	ENST00000428084.6	c.5481+1646C>G		intron_variant		5	NM_001363540.2	P3

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6791 AN: 152044 Hom.: 182 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.0812

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0373

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0446 AC: 6791 AN: 152162 Hom.: 181 Cov.: 32 AF XY: 0.0438 AC XY: 3261 AN XY: 74384

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.0273

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.0318

Gnomad4 SAS AF: 0.0817

Gnomad4 FIN AF: 0.0415

Gnomad4 NFE AF: 0.0388

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0416 Hom.: 18

Bravo AF: 0.0425

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.1
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs867915; hg19: chr7-111370636;